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Michael Newton

Publications and source records attributed to Michael Newton.

10 recordsLinked to original sources
PubMed2006

Controlled drug release from pellets containing water-insoluble drugs dissolved in a self-emulsifying system.

The aim of the study was to provide a controlled release system, which could be used for the oral administration of highly water-insoluble drugs. Pellets have been prepared by extrusion/spheronization containing two model drugs (methyl and propyl parabens) of low water solubility. One type of pellets contained the drugs mixed with lactose and microcrystalline cellulose (MCC) and the other types of pellets contained the model drugs dissolved in a self-emulsifying system (4.8%) consisting of equal parts of mono-diglycerides and polysorbate 80 and MCC. Pellets of all types in the same size fraction (1.4-2.0 mm) were coated to different levels of weight gain, with ethylcellulose, talc and glycerol. A sample of pellets containing methyl parabens in the self-emulsifying system was pre-coated with a film of hydroxypropylmethyl cellulose from an aqueous solution and then coated as above. Dissolution experiments established that the presence of the self-emulsifying system enhanced the drug release of both model drugs and that the film coating considerably reduced the drug release from pellets made with just water, lactose and MCC. The coating reduced the drug release from the pellets containing the self-emulsifying system to a lesser extent but in relation to the quantity of coat applied to the pellets. The application of a sub-coating of hydroxypropylmethyl cellulose was able to reduce the release rate of methyl parabens self-emulsifying system ethyl cellulose coated pellets. Thus, the formulation approach offers the possibility of formulating and controlling the in vitro release of water-insoluble drugs from solid oral dosage forms.

Capsules↗
PubMed2006

Eccentric utilization ratio: effect of sport and phase of training.

The eccentric utilization ratio (EUR), which is the ratio of countermovement jump (CMJ) to static jump (SJ) performance, has been suggested as a useful indicator of power performance in athletes. The purpose of the study was to compare the EUR of athletes from a variety of different sports and during different phases of training. A total of 142 athletes from rugby union, Australian Rules Football, soccer, softball, and field hockey were tested. Subjects performed both CMJ and SJ on a force plate integrated with a position transducer. The EUR was measured as the ratio of CMJ to SJ for jump height and peak power. The rugby union, Australian Rules Football, and hockey athletes were tested during off-season and preseason to provide EUR data during different phases of training. For men, EUR for soccer, Australian Rules Football, and rugby was greater than softball (effect size range, 0.83-0.92). For women, EUR for soccer was greater than field hockey and softball (0.86- 1.0). There was a significant difference between the jump height and peak power method for the Australian Rules Football, rugby, and field hockey tests conducted preseason (p < 0.05). For field hockey, there was a significant increase in EUR from off-season to preseason. Athletes in sports such as soccer, rugby union, and Australian Rules Football appear to have higher EUR values, which reflects the greater reliance on stretch shortening activities in these sports. It does appear that EUR can be used to track changes in training with the values significantly increasing from off-season to preseason. The EUR provides the practitioner with information about the performance of athletes and appears to be sensitive to changes in the type of training being undertaken.

Adult↗
PubMed2004

Comparative bioavailability study in dogs of a self-emulsifying formulation of progesterone presented in a pellet and liquid form compared with an aqueous suspension of progesterone.

A pellet formulation of progesterone in a self-emulsifying system (SES) was prepared by the process of extrusion/spheronization to provide a good in vitro drug release (100% within 30 min, T(50%) at 13 min). A three-way randomized crossover study was performed in six fasted male beagle dogs with these pellets and the same SES liquid formulation, both contained in a hard shell capsule, and an aqueous suspension. The same dose of progesterone (16 mg) in pellets and in the SES liquid formulation resulted in similar AUC, C(max) and T(max) values, estimated from progesterone plasma levels by (125)I radioimmunoassay. Although the maximum absorption was slightly retarded (0.5 to 1 h) by SES (pellets and liquid), AUC and C(max) were approximately seven and nine times greater then those obtained when an aqueous suspension formulation of the same dose of progesterone was administered to the same dogs. These results showed that it was possible to improve the bioavailability of the poorly soluble, poorly permeable progesterone when administered in SES. Moreover, presenting the progesterone in the form of a pellet did not prevent the release of the drug in vivo. These data demonstrate the utility of extrusion/spheronization in delivering a nonaqueous system in a novel solid dosage form.

Animals↗
PubMed2004

Long overlooked historical information on Agent Orange and TCDD following massive applications of 2,4,5-T-containing herbicides, Eglin Air Force Base, Florida.

BACKGROUND: From 1961-1971, The Air Development Test Center, Eglin Air Force Base (AFB), Florida, developed, tested, and calibrated the aerial spray systems used in support of Operation RANCH HAND and the US Army Chemical Corps in Vietnam. Twenty major test and evaluation projects of aerial spray equipment were conducted on four fully instrumented test grids, each uniquely arrayed to match the needs of fixed-wing, helicopter, or jet aircraft. Each of the grids was established within the boundary of Test Area 52A of the Eglin Reservation. METHODS: The tests, conducted under climatic and environmental conditions similar to those in Vietnam, included the use of the military herbicides (Agents) Orange, Purple, White, and Blue. Approximately 75,000 kg of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and 76,000 kg of 2,4-dichlorophenoxyacetic acid (2,4-D) were aerially disseminated on an area of less than 3 km2 during the period 1962-1970. Data from the analysis of archived samples suggested that an estimated 3.1 kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), present as a contaminant, were aerially released in the test area. Because most of the vegetation had been removed before establishing the test site in 1961, there was an opportunity to follow ground-based residues independent of canopy interception, and the resulting high solar exposure of initial residues. Studies of the soils, fauna, flora, and aquatic ecosystems of the test grids and associated perimeters of Test Area C-52A (an area totally more than 8 km2) were initiated in 1969 and concluded in 1984. RESULTS AND DISCUSSION: Data from soil samples collected from 1974 through 1984 suggested that less than one percent of the TCDD that was present in soil when sampling began persisted through the ten-year period of sampling. More than 340 species of organisms were observed and identified within the test area. More than 300 biological samples were analyzed for TCDD and detectable residues were found in 16 of 45 species examined. Examination of the ecological niches of the species containing TCDD residues suggested each was in close contact with contaminated soil. Indepth field studies, including anatomical, histological and ultrastructural examinations, spanning more than 50 generations of the Beachmouse, Peromyscus polionotus, demonstrated that continual exposure to soil concentrations of 0.1 to 1.5 parts-per-billion (ng/g) of TCDD, had minimal effects upon the health and reproduction of this species. CONCLUSIONS: Since Agent Orange with its associated TCDD contaminant was aerially disseminated on the test grids, Test Area C-52A provided a 'field laboratory' for what may have happened in Vietnam, had there been no intercepting forest cover. However, in Vietnam a 'typical' mission would have disseminated 14.8 kg of 2,4,5-T/ha, most of which was intercepted by the forest canopy, versus the 876 kg 2,4,5-T/ha on the test grid at Eglin. Moreover, each hectare on the Eglin test grid received at least 1,300 times more TCDD than a hectare sprayed with Agent Orange in Vietnam. The disappearance or persistence of TCDD is dependent upon how it enters the ecosystem. Spray equipment test and evaluations missions at Eglin were generally scheduled and conducted with environmental conditions that were optimal for spray operations. This suggests that conditions favorable for dissemination of herbicide were the same conditions favorable for photodegradation of TCDD. It was likely that 99 percent of the TCDD never persisted beyond the day of application. No long-term adverse ecological effects were documented in these studies despite the massive quantities of herbicides and TCDD that were applied to the site. Reviews by the US Environmental Protection Agency and the National Academy of Sciences' Institute of Medicine did not address the fate of Agent Orange and TCDD as described in these studies from Eglin AFB, Florida.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed2004

Environmental fate and bioavailability of Agent Orange and its associated dioxin during the Vietnam War.

BACKGROUND: In 1996, the Committee on the Assessment of Wartime Exposure to Herbicides in Vietnam of the National Academy of Sciences' Institute of Medicine (IOM) issued a report on an exposure model for use in epidemiological studies of Vietnam veterans. This exposure model would consider troop locations based on military records; aerial spray mission data; estimated ground spraying activity; estimated exposure opportunity factors; military indications for herbicide use; and considerations of the composition and environmental fate of herbicides, including changes in the TCDD content of the herbicides over time, the persistence of TCDD and herbicides in the environment, and the degree of likely penetration of the herbicides into the ground. When the final report of the IOM Committee was released in October 2003, several components of the exposure model envisioned by the Committee were not addressed. These components included the environmental fate of the herbicides, including changes in the TCDD content over time, the persistence of TCDD and herbicides in the environment, and the degree of likely penetration of herbicides into the ground. This paper is intended to help investigators understand better the fate and transport of herbicides and TCDD from spray missions, particularly in performing epidemiological studies. METHODS: This paper reviews the published scientific literature related to the environmental fate of Agent Orange and the contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and discusses how this affected the potential exposure to TCDD of ground troops in Vietnam. Specifically, the mechanisms of dissipation and degradation as they relate to environmental distribution and bioavailability are addressed. RESULTS: The evaluation of the spray systems used to disseminate herbicides in Vietnam showed that they were capable of highly precise applications both in terms of concentrations sprayed and area treated. Research on tropical forest canopies with leaf area indices (a measure of foliage density) from 2 to 5 indicated that the amount of herbicide and associated TCDD reaching the forest floor would have been between 1 and 6% of the total aerial spray. Studies of the properties of plant surface waxes of the cuticle layer suggested that Agent Orange, including the TCDD, would have dried (i.e., be absorbed into the wax layer of the plant cuticle) upon spraying within minutes and could not be physically dislodged. Studies of Agent Orange and the associated TCDD on both leaf and soil surface have demonstrated that photolysis by sunlight would have rapidly decreased the concentration of TCDD, and this process continued in shade. Studies of 'dislodgeable foliar residues' (DFR, the fraction of a substance that is available for cutaneous uptake from the plant leaves) showed that only 8% of the DFR was present 1 hr after application. This dropped to 1% of the total 24 hrs after application. Studies with human volunteers confirmed that after 2 hrs of saturated contact with bare skin, only 0.15-0.46% of 2,4,5-T, one of the phenoxy acetic acid compounds that was an active ingredient of Agent Orange, entered the body and was eliminated in the urine. CONCLUSIONS: The prospect of exposure to TCDD from Agent Orange in ground troops in Vietnam seems unlikely in light of the environmental dissipation of TCDD, little bioavailability, and the properties of the herbicides and circumstances of application that occurred. Photochemical degradation of TCDD and limited bioavailability of any residual TCDD present in soil or on vegetation suggest that dioxin concentrations in ground troops who served in Vietnam would have been small and indistinguishable from background levels even if they had been in recently treated areas. Laboratory and field data reported in the literature provide compelling evidence on the fate and dislodgeability of herbicide and TCDD in the environment. This evidence of the environmental fate and poor bioavailability of TCDD from Agent Orange is consistent with the observation of little or no exposure in the veterans who served in Vietnam. Appreciable accumulation of TCDD in veterans would have required repeated long-term direct skin contact of the type experienced by United States (US) Air Force RANCH HAND and US Army Chemical Corps personnel who handled or otherwise had direct contact with liquid herbicide, not from incidental exposure under field conditions where Agent Orange had been sprayed.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed2004

A prospective, randomized, study comparing early percutaneous dilational tracheotomy to prolonged translaryngeal intubation (delayed tracheotomy) in critically ill medical patients.

OBJECTIVE: The timing of tracheotomy in patients requiring mechanical ventilation is unknown. The effects of early percutaneous dilational tracheotomy compared with delayed tracheotomy in critically ill medical patients needing prolonged mechanical ventilation were assessed. DESIGN: Prospective, randomized study. SETTING: Medical intensive care units. PATIENTS: One hundred and twenty patients projected to need ventilation >14 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were prospectively randomized to either early percutaneous tracheotomy within 48 hrs or delayed tracheotomy at days 14-16. Time in the intensive care unit and on mechanical ventilation and the cumulative frequency of pneumonia, mortality, and accidental extubation were documented. The airway was assessed for oral, labial, laryngeal, and tracheal damage. Early group showed significantly less mortality (31.7% vs. 61.7%), pneumonia (5% vs. 25%), and accidental extubations compared with the prolonged translaryngeal group (0 vs. 6). The early tracheotomy group spent less time in the intensive care unit (4.8 +/- 1.4 vs. 16.2 +/- 3.8 days) and on mechanical ventilation (7.6 +/- 2.0 vs. 17.4 +/- 5.3 days). There was also significantly more damage to mouth and larynx in the prolonged translaryngeal intubation group. CONCLUSIONS: This study demonstrates that the benefits of early tracheotomy outweigh the risks of prolonged translaryngeal intubation. It gives credence to the practice of subjecting this group of critically ill medical patients to early tracheotomy rather than delayed tracheotomy.

Procedural Sedation↗
PubMed2004

Changes in inflammatory mediators following eccentric exercise of the elbow flexors.

The aims of this study were to examine the plasma concentrations of inflammatory mediators including cytokines induced by a single bout of eccentric exercise and again 4 weeks later by a second bout of eccentric exercise of the same muscle group. Ten untrained male subjects performed two bouts of the eccentric exercise involving the elbow flexors (6 sets of 5 repetitions) separated by four weeks. Changes in muscle soreness, swelling, and function following exercise were compared between the bouts. Blood was sampled before, immediately after, 1 h, 3 h, 6 h, 24 h (1 d), 48 h (2 d), 72 h (3 d), 96 h (4 d) following exercise bout to measure plasma creatine kinase (CK) activity, plasma concentrations of myoglobin (Mb), interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1ra), IL-4, IL-6, IL-8, IL-10, IL-12p40, tumor necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor (G-CSF), myeloperoxidase (MPO), prostaglandin E2 (PGE2), heat shock protein (HSP) 60 and 70. After the first bout, muscle soreness increased significantly, and there was also significant increase in upper arm circumference; muscle function decreased and plasma CK activity and Mb concentration increased significantly. These changes were significantly smaller after the second bout compared to the first bout, indicating muscle adaptation to the repeated bouts of the eccentric exercise. Despite the evidence of greater muscle damage after the first bout, the changes in cytokines and other inflammatory mediators were quite minor, and considerably smaller than that following endurance exercise. These results suggest that eccentric exercise-induced muscle damage is not associated with the significant release of cytokines into the systemic circulation. After the first bout, plasma G-CSF concentration showed a small but significant increase, whereas TNF-alpha and IL-8 showed significant decreases compared to the pre-exercise values. After the second bout, there was a significant increase in IL-10, and a significant decrease in IL-8. In conclusion, although there was evidence of severe muscle damage after the eccentric exercise, this muscle damage was not accompanied by any large changes in plasma cytokine concentrations. The minor changes in systemic cytokine concentration found in this study might reflect more rapid clearance from the circulation, or a lack of any significant metabolic or oxidative demands during this particular mode of exercise. In relation to the adaptation to the muscle damage, the anti-inflammatory cytokine IL-10 might work as one of the underlying mechanisms of action.

Adolescent↗
PubMed2003

New-onset diabetes and ketoacidosis with atypical antipsychotics.

Information from the Ohio Department of Mental Health (ODMH) database was reviewed retrospectively to identify patients at the Cincinnati center treated with an atypical antipsychotic and who had also been evaluated or treated for diabetes mellitus. Blood glucose levels, glucose tolerance, or other evaluations of diabetes had been conducted in 14 of the 126 patients treated with atypical antipsychotics. In 11 of the 14, new-onset, acute, and marked glucose intolerance developed after treatment with clozapine, olanzapine or quetiapine. Of these, six patients required insulin therapy (four only transiently) and five patients developed diabetic ketoacidosis (DKA). Also, glucose metabolism was labile in all cases, and was transient in two cases with subsequent resolution despite on-going antipsychotic therapy. Certain atypical antipsychotics may be associated with new-onset glucose intolerance, including acute diabetes and ketoacidosis. Monitoring for changes in blood glucose levels in patients taking atypical antipsychotics may be indicated. More systematic study data are clearly needed.

Adult↗